コバヤシ ヒロシ   KOBAYASHI Hiroshi
  小林 弘
   所属   医学部 医学科(東京女子医科大学病院)
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Fibroblast sheets co-cultured with endothelial progenitor cells improve cardiac function of infarcted hearts.
掲載誌名 正式名:Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs
略  称:J Artif Organs
ISSNコード:(1434-7229)1434-7229(Linking)
掲載区分国外
巻・号・頁 11(3),141-7頁
著者・共著者 Kobayashi Hiroshi†, Shimizu Tatsuya, Yamato Masayuki, Tono Kayoko, Masuda Haruchika, Asahara Takayuki, Kasanuki Hiroshi, Okano Teruo*
発行年月 2008/09
概要 We have already confirmed that cell sheet transplantation can improve damaged heart function via continuous cytokine secretion. In this study, we hypothesized that cytokine-secreting cell sheets co-cultured with an endothelial cell source may be more effective for repairing ischemic myocardium. Confluent rat fibroblasts cultured on temperature-responsive culture dishes were harvested as contiguous cell sheets by temperature reduction. Green fluorescent protein (GFP)-positive endothelial progenitor cells (EPCs) were seeded on fibroblast sheets to create co-cultured cell sheets, and sandwich-like constructs were engineered by stacking of the co-cultured cell sheets. These constructs were transplanted into rat myocardial infarction models. Cardiac function and histology were assessed in four groups: the sham operation (C) group, the isolated EPC injection (E) group, the transplantation of triple-layer fibroblast sheets (F) group, and the transplantation of triple-layer sandwich-like constructs (E + F) group. Echocardiography showed significant improvement of the fractional shortening in the E + F group in comparison with the C group (0.25 +/- 0.05 vs. 0.16 +/- 0.02). On histological examination, significantly less connective tissue formation was observed in the E, F, and E + F groups when compared to the C group (C, E, F, and E + F groups: 53 +/- 2%, 41 +/- 4%, 40 +/- 4%, and 32 +/- 7%, respectively). Additionally, increased blood vessel formation was detected in the E, F, and E + F groups compared with the C group (C, E, F, and E + F groups: 1.9% +/- 0.6%, 6.7% +/- 0.6%, 7.8% +/- 0.9%, and 10.2% +/- 2.4%, respectively). Furthermore, GFP-staining demonstrated that the newly formed blood vessels were composed of the co-cultured EPCs. Transplantation of cell sheets co-cultured with an endothelial cell source may be a new therapeutic strategy for myocardial tissue regeneration.
DOI 10.1007/s10047-008-0421-8
PMID 18836875